NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance.
Jin-Ming YangYijie RenAnil KumarXiaofang XiongJugal Kishore DasHao-Yun PengLiqing WangXingcong RenYi ZhangCheng JiYan ChengLi ZhangRobert C AlanizPaul de FigueiredoDeyu FangHongwei ZhouXiaoqi LiuJianlong WangJianxun SongPublished in: Science advances (2022)
We report here that nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the Broad-complex, Tramtrack, Bric-a-brac/poxvirus and zinc finger (BTB/POZ) gene family, is a negative regulator of FoxP3 in regulatory T cells (T regs ) and a critical determinant of immune tolerance. Phenotypically, NAC1 -/- mice showed substantial tolerance to the induction of autoimmunity and generated a larger amount of CD4 + T regs that exhibit a higher metabolic profile and immune-suppressive activity, increased acetylation and expression of FoxP3, and slower turnover of this transcription factor. Treatment of T regs with the proinflammatory cytokines interleukin-1β or tumor necrosis factor-α induced a robust up-regulation of NAC1 but evident down-regulation of FoxP3 as well as the acetylated FoxP3. These findings imply that NAC1 acts as a trigger of the immune response through destabilization of T regs and suppression of tolerance induction, and targeting of NAC1 warrants further exploration as a potential tolerogenic strategy for treatment of autoimmune disorders.
Keyphrases
- regulatory t cells
- transcription factor
- dendritic cells
- nuclear factor
- immune response
- dna binding
- toll like receptor
- genome wide analysis
- poor prognosis
- rheumatoid arthritis
- drug delivery
- metabolic syndrome
- inflammatory response
- risk assessment
- combination therapy
- body composition
- high glucose
- skeletal muscle
- smoking cessation
- binding protein
- bone mineral density
- human health